Sociability and amygdala-dependent memory deficits in Dishevelled mutant mice
Wednesday, Nov 13, 2013, 8:00 AM - 9:00 AM
++C.07.a. Autism: Genetic and animal models
*B. A. BABINEAU
, J. NAKATANI
, H. BELINSON
, A. WYNSHAW-BORIS
Dept. of Pediatrics and Inst. of Human Genet., Univ. of California San Francisco, San Francisco, CA;
Biomed. Resonance Sci. Ctr., Shiga Univ. of Med. Sci., Seta-Tsukinowa, Otsu, Shiga, Japan;
Dept. of Genet. and Genome Sci., Case Western Reserve Univ., Cleveland, OH
Mice with mutations in
1) were the first mutant mice to display behavioral abnormalities in social domains (Lijam et al. 1997, Long et al., 2004). In mammals, three highly homologous
) genes have been identified:
(Klingensmith et al., 1996; Sussman et al., 1994; Tsang et al., 1996). Here we evaluate mice heterozygous for
+/-), mice with a homozygous knockout of
-/-) and mice with mutations in both
1 -/-3+/-) to further examine the role of each of these genes in social behavior and related behavioral domains. In addition,
mutant mice expressing
2 transgenes specific to either the Wnt or Wnt/PCP pathway were evaluated and compared on these behavioral tasks to determine the pathway responsible for any phenotypic effects.
1-/-3+/- mutants all display defective sociability on the three chambered social approach task, measured by time spent sniffing the novel mouse. The wild-type
2 transgene rescued defective sociability in
1-/-3+/- mutants. The PCP-deficient
2 transgene also rescued the defective sociability in the
1-/-3+/- double mutants. In the fear-conditioning task, which assesses amygdala-dependent memory formation,
3+/- mutants did not display any deficits in the amount of time spent freezing in either the contextual or cued condition.
1-/- mutants tended to freeze less than the wild-type controls in contextual fear conditioning. All
1-/- mutants expressing transgenes displayed freezing levels similar to wild-type controls.
1-/-3+/- double mutants also displayed diminished freezing behavior in contextual fear conditioning. This deficit was not rescued by the wild-type
2 transgene. The PCP-deficient
2 transgene, did however, appear to rescue the amygdala-dependent memory deficit in the
1-/-3+/- double mutants. Histological findings suggest that the amygdala of
mutants display increased expression of GABAergic interneurons and abnormalities of dendritic branching. We are currently testing whether these GABAergic and dendritic abnormalities are rescued by any of the transgenes. We expect that these analyses will provide insight into the role(s) of
in social behavior and fear conditioning and the mechanism by which these phenotypic effects occur.
NIH Grant 9R01 NS073159-08
NIH Grant 2T32 GM007085-32
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